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PubMed2002

Differential discrimination of fast and slow synaptic waveforms by two low-voltage-activated calcium channels.

Electrophysiological analysis of human embryonic kidney 293 cells stably expressing recombinant channels was used to compare how the biophysical properties of the low-voltage-activated Ca(2+) channels encoded by the alpha(1G) (Ca(V)3.1) or alpha(1I) (Ca(V)3.3) subunits shape their responses to excitatory synaptic potentials. In medium containing 2 mM extracellular Ca(2+) standard current-voltage relationships demonstrated both channel types to be clearly low-voltage activated with significant slowly activating current responses being observed at -66 mV. At all test potentials examined, activation of Ca(V)3.3 was substantially slower than that of Ca(V)3.1. To probe how these different T-type channels might respond to excitatory postsynaptic potentials (EPSPs), mock EPSPs with different kinetic profiles were created from the sum of exponentials. These waveforms were then used as command templates in voltage-clamp experiments. Ca(V)3.1-mediated channels responded effectively to both rapidly decaying mock EPSPs and slowly decaying EPSPs. In contrast, Ca(V)3.3-mediated channels were poorly gated by rapidly decaying EPSPs but were effectively activated by the more prolonged synaptic response. When activated with mock EPSPs Ca(V)3.3-mediated currents were more resistant to steady-state depolarisation of the pre-stimulus holding potential. Ca(V)3.3 currents were also more resistant to repetitive application of prolonged EPSPs, which caused substantial inactivation of Ca(V)3.1-mediated currents. The addition of a single mock action potential to the peak of a rapidly decaying EPSP voltage-clamp template greatly enhanced the currents produced by either Ca(V)3.1 or Ca(V)3.3-expressing cells. This facilitatory effect was considerably greater for Ca(V)3.3-mediated channels. From these data we suggest that the slow activation kinetics of Ca(V)3.3-mediated T-type channels enable them to respond selectively to either slow or suprathreshold synaptic potentials.

Animals↗
PubMed1997

Guinea pig pancreatic neurons: morphology, neurochemistry, electrical properties, and response to 5-HT.

The morphology, neurochemistry, and electrical properties of guinea pig pancreatic neurons were determined. The majority of neurons expressed choline acetyltransferase (ChAT) immunoreactivity; however, ChAT-negative neurons were also found. Both cholinergic and noncholinergic neurons expressed nitric oxide synthase (NOS) immunoreactivity. Three types of pancreatic neurons were distinguished. Phasic neurons fired action potentials (APs) at the onset of depolarizing current pulse, tonic neurons spiked throughout the duration of a suprathreshold depolarizing pulse, and APs could not be generated in nonspiking neurons, even though they did receive synaptic input. APs were tetrodotoxin sensitive, and all types of neurons received fast and slow excitatory postsynaptic potentials (EPSPs). Fast EPSPs had cholinergic and noncholinergic components. The majority of pancreatic neurons appeared to innervate the acini. NOS- and/or neuropeptide Y-immunoreactive phasic and tonic neurons were found. Microejection of 5-hydroxytryptamine (5-HT) caused a slow depolarization that was inhibited by the 5-HT1P antagonist N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide and mimicked by the 5-HT1P agonist 6-hydroxyindalpine. A pancreatic 5-HT transporter was located, and inhibition of 5-HT uptake by fluoxetine blocked slow EPSPs in 5-HT-responsive neurons by receptor desensitization.

Action Potentials↗
PubMed1998

Synaptic inputs to stellate cells in the ventral cochlear nucleus.

Auditory information is carried from the cochlear nuclei to the inferior colliculi through six parallel ascending pathways, one of which is through stellate cells of the ventral cochlear nuclei (VCN) through the trapezoid body. To characterize and identify the synaptic influences on T stellate cells, intracellular recordings were made from anatomically identified stellate cells in parasagittal slices of murine cochlear nuclei. Shocks to the auditory nerve consistently evoked five types of synaptic responses in T stellate cells, which reflect sources intrinsic to the cochlear nuclear complex. 1) Monosynaptic excitatory postsynaptic potentials (EPSPs) that were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX), an antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, probably reflected activation by auditory nerve fibers. Electrophysiological estimates indicate that about five auditory nerve fibers converge on one T stellate cell. 2) Disynaptic, glycinergic inhibitory postsynaptic potentials (IPSPs) arise through inhibitory interneurons in the VCN or in the dorsal cochlear nucleus (DCN). 3) Slow depolarizations, the source of which has not been identified, that lasted between 0.2 and 1 s and were blocked by -2-amino-5-phosphonovaleric acid (APV), the N-methyl-D-aspartate (NMDA) receptor antagonist. 4) Rapid, late glutamatergic EPSPs are polysynaptic and may arise from other T stellate cells. 5) Trains of late glycinergic IPSPs after single or repetitive shocks match the responses of D stellate cells, showing that D stellate cells are one source of glycinergic inhibition to T stellate cells. The source of late, polysynaptic EPSPs and IPSPs was assessed electrophysiologically and pharmacologically. Late synaptic responses in T stellate cells were enhanced by repetitive stimulation, indicating that the interneurons from which they arose should fire trains of action potentials in responses to trains of shocks. Late EPSPs and late IPSPs were blocked by APV and enhanced by the removal of Mg2+, indicating that the interneurons were driven at least in part through NMDA receptors. Bicuculline, a gamma-aminobutyric acid-A (GABAA) receptor antagonist, enhanced the late PSPs, indicating that GABAergic inhibition suppresses both the glycinergic interneurons responsible for the trains of IPSPs in T-stellate cells and the interneuron responsible for late EPSPs in T stellate cells. The glycinergic interneurons that mediate the series of IPSPs are intrinsic to the ventral cochlear nucleus because long series of IPSPs were recorded from T stellate cells in slices in which the DCN was removed. These experiments indicate that T stellate cells are a potential source of late EPSPs and that D stellate cells are a potential source for trains of late IPSPs.

Action Potentials↗
PubMed2006

Self-modeling structure of evoked postsynaptic potentials.

With the simplicity of the synaptic structure and physiology at neuromuscular junctions (NMJs) of crayfish and the given transmitter being released in quantal packets, a detailed assessment in the fundamental processes of chemical synaptic transmission is possible. Since the quantal event is the basic element of transmission, we consider an approach to further understand the characteristics of quantal responses. In this study, we introduce a method for combining information across excitatory postsynaptic potentials (EPSPs) that are quantal in nature. The method is called self-modeling regression, known in the statistics literature as SEMOR. This method illustrates that the differing timing and heights of EPSPs can be described with four coefficients measuring affine (shift and scale) transformations of the x and y axes. We demonstrate that this relationship allows us to provide a unified schema for the many functionals currently used in the literature, such as peak amplitude, tau, latency, area under the curve, or decay time. Computer code in R is available on the internet to perform the analysis.

Animals↗
PubMed1999

Synaptic transmission and hippocampal long-term potentiation in transgenic mice expressing FAD-linked presenilin 1.

Mutations in two related genes, presenilin 1 and presenilin 2 (PS1 and PS2), cause a subset of early-onset familial Alzheimer's disease (FAD). PS1 is expressed in a variety of neuronal and peripheral tissues, including neuronal populations known to be at risk in Alzheimer's disease such as CA1 hippocampal neurons. To examine whether FAD-linked mutations in PS1 directly influence the physiology of learning and memory, we measured the field excitatory postsynaptic potential (fEPSP) at the Schaffer collateral-CA1 synapse in hippocampal slices. Basal synaptic transmission and long-term potentiation (LTP) were examined in neurons of transgenic mice expressing wild-type human PS1 (WtTg) and FAD-linked A246E PS1 variant (MTg) and in neurons of nontransgenic littermates (NTg). Several measures of basal synaptic transmission were unaltered in WtTg and MTg compared to NTg mice, including maximum fEPSP slope, maximum fEPSP amplitude, maximum fiber volley amplitude, and the function relating fiber volley amplitude to fEPSP slope, an index of basal synaptic strength. In addition, paired-pulse facilitation was not changed. However, upon theta burst stimulation or high-frequency stimulation, input-specific LTP in MTg animals had a larger initial amplitude and was more persistent than that in WtTg or NTg animals. These data suggest that the FAD-linked A246E variant of PS1 leads to higher degree of LTP induction in mice.

Action Potentials↗
PubMed2001

Epileptiform activity in the nucleus accumbens induced by GABA(A) receptor antagonists in rat forebrain slices is of cortical origin.

Extracellularly recorded field potentials, evoked by stimulation of cortico-nucleus accumbens border, were recorded in the nucleus accumbens (NAcc) in horizontal slices of rat ventral forebrain. The field excitatory postsynaptic potential (EPSP) event (N2) was calcium dependent, blocked by tetrodotoxin (1 microM), and reduced by over 70% by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 microM), the antagonist of AMPA-type glutamate receptors. The EPSP amplitude was enhanced by either of the GABA(A) receptor antagonists, picrotoxin (10 microM; by 252+/-33%, n=18) and bicuculline methiodide (20 microM; by 216+/-34%, n=4). Additionally, picrotoxin (3-50 microM) and bicuculline methiodide (20 microM) promoted epileptiform activity within the NAcc, manifest as the emergence of additional late components, N3, N4 and N5, in the evoked synaptic waveform. In slices with the frontal cortex removed, picrotoxin (10-50 microM) and bicuculline methiodide (20 microM) were unable to promote epileptiform activity within the NAcc, although a smaller increase in the peak amplitude of the field EPSP (163+/-18%, n=6) was observed at the highest concentrations of picrotoxin (50 microM). Histological examination of the slice demonstrated that in such decorticated slices, the piriform cortex (PC) had been removed. We propose that stimulation of the cortico-NAcc border not only evokes an orthodromic EPSP in the NAcc, but also causes antidromic activation of cortical tissue. Disinhibition by GABA(A) antagonists of circuits intrinsic to the cortex, possibly the piriform cortex, is the principal cause of the facilitation of the EPSP and of regenerative epileptiform activity in NAcc evoked by stimulation of cortical input.

Animals↗
PubMed2026

Altered Excitation-Inhibition Balance and mGluR1/5-Driven Plasticity in the Motor Cortical Surface in a Rat Model of Parkinson's Disease.

Parkinson's disease (PD) is characterized by progressive dopaminergic degeneration and maladaptive motor cortical plasticity. However, the cellular pathways underlying cortical surface activity in the primary motor cortex (M1) remain unclear, despite serving as a potential target for electrotherapy. We investigated the excitatory-inhibitory (E-I) balance and synaptic plasticity of superficial M1 circuits in a unilateral 6-hydroxydopamine (6-OHDA)-induced rat model of PD. Using extracellular local field potential and whole-cell patch recordings from the contralateral and ipsilateral M1 hemispheres of hemi-parkinsonian rats, we observed a significantly elevated field excitatory postsynaptic potential (fEPSP) input-output function but unchanged intrinsic neuronal excitability in the M1 superficial layer. An altered relative contribution between alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and N-methyl-D-aspartate receptor (NMDAR)-mediated transmission was reflected by a significantly increased AMPA/NMDA ratio. Markedly reduced inhibitory synaptic tone was also evidenced by the decreased amplitude and frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), supporting an E-I imbalance favoring excitation in PD. Furthermore, group I metabotropic glutamate receptor (mGluR1/5)-dependent long-term depression (LTD) was abolished in the ipsilateral PD hemisphere, whereas NMDAR-dependent LTD remained intact. In summary, dopamine depletion appears to enhance network excitation and disrupt mGluR1/5-mediated control of M1 surface circuitry. Our findings identify altered cortical surface mGluR-dependent plasticity in the hemi-parkinsonian model; however, the relationship between these electrophysiological alterations and individual motor outcomes remains to be determined.

Animals↗
PubMed2003

Septal modulation of excitatory transmission in hippocampus.

Application of the acetylcholinesterase inhibitor physostigmine to conventional hippocampal slices caused a significant reduction of field excitatory postsynaptic potentials (EPSPs) elicited by single pulse stimulation to the medial perforant path. Similar but smaller effects were obtained in the lateral perforant path and other excitatory pathways within hippocampus. The reductions were blocked by atropine, were not accompanied by evident changes in the EPSP waveform, and were eliminated by lesions to the cholinergic septo-hippocampal projections. Antidromic responses to mossy fiber stimulation, recorded in stratum granulosum, were not affected by the drug. However, paired-pulse facilitation was reliably increased, indicating that the depressed synaptic responses were secondary to reductions in transmitter release. The absence of cholinergic axo-axonic connections in the molecular layer suggests that physostigmine reduces presynaptic release by increasing retrograde signaling from the granule cells. In accord with this, an antagonist of the CB1 cannabinoid receptor eliminated the effects of physostigmine on synaptic responses, while an antagonist of the presynaptically located m2 muscarinic acetylcholine receptor did not. This is in contrast to previously reported effects involving application of cholinergic agonists, in which presynaptic inhibition likely results from direct activation of presynaptically located muscarinic receptors. In summary, it is proposed that the cholinergic inputs from the septum to the middle molecular layer modulate, via endocannabinoid release, the potency of the primary excitatory afferent of hippocampus.

Animals↗
PubMed1989

Multiple effects of phorbol esters in the rat spinal dorsal horn.

Spinal cord slice preparation and intracellular recording techniques were used to examine the effects of phorbol esters on the sodium- and calcium-dependent action potentials, the excitatory synaptic transmission, the basal (resting) and the dorsal root stimulation-evoked release of 9 endogenous amino acids, including glutamate and aspartate, and the responsiveness of the rat dorsal horn neurons to excitatory amino acids (glutamic, kainic, quisqualic, and N-methyl-D-aspartic). 4-beta-Phorbol-12, 13-dibutyrate and 4-beta-phorbol-12, 13-diacetate produced minor alterations in membrane potential and resistance, but they broadened the sodium-dependent action potential and reduced the duration of the calcium-dependent action potential. In addition, phorbol esters caused a marked and long-lasting increase in the amplitude and the duration of excitatory postsynaptic potentials (EPSPs) evoked in dorsal horn neurons by orthodromic stimulation of a lumbar dorsal root. Phorbol esters produced a brief increase in the basal and electrically evoked release of endogenous excitatory (glutamic, aspartic) and inhibitory amino acids (glycine, GABA). In addition, the rates of release of alanine, serine, and threonine were also elevated. In the presence of TTX, phorbol esters selectively enhanced, in a reversible manner, the depolarizing responses of dorsal horn neurons to N-methyl-D-aspartic acid and L-glutamate but not the responses to kainic or quisqualic acids. The potentiation of the NMDA response was blocked by APV, a specific NMDA receptor antagonist. Thus, phorbol esters appear to enhance excitatory synaptic transmission in the rat spinal dorsal horn slice preparation by acting both at pre- and postsynaptic sites. Phorbol esters could potentiate excitatory synaptic transmission by acting predominantly at a postsynaptic site (NMDA receptor), since the duration of the increased responsiveness of dorsal horn neurons to glutamate and NMDA correlates better with the enhancement of EPSPs than with the increased release of the stimulation-evoked glutamate and aspartate. The increased release of endogenous amino acids is consistent with a presynaptic (terminal) site of action, but it could also be explained by enhanced interneuronal activity. Although our results suggest that in the rat spinal dorsal horn protein kinase C may have a role in controlling the release of putative excitatory and inhibitory neurotransmitters and may also be involved in the regulation of postsynaptic NMDA receptors, the identity of endogenous substance(s) participating in these effects is presently unknown.

Action Potentials↗
PubMed2002

Effects of vigabatrin on epileptiform abnormal discharges in hippocampal CA3 neurons of spontaneously epileptic rats (SER).

Vigabatrin, a gamma-amino butyric acid (GABA) transaminase inhibitor, is known to inhibit partial epilepsy in humans. The spontaneously epileptic rat (SER), a double mutant (zi/zi, tm/tm), exhibits both tonic convulsion and absence-like seizures from the age of 8 weeks. Hippocampal CA3 pyramidal neurons in SER show a long-lasting depolarization shift with accompanying repetitive firing when a single stimulus is delivered to the mossy fibers in slice preparations. The effects of vigabatrin on the abnormal excitability of hippocampal CA3 pyramidal neurons in SER were examined to elucidate the mechanism underlying the antiepileptic action of the drug. Intracellular recordings were performed in 24 hippocampal slice preparations of 20 SER aged 8-17 weeks old. Bath application of vigabatrin (1 mM) inhibited the depolarizing shifts with repetitive firing induced by mossy fiber stimulation in 15 min without affecting the first spike and resting membrane potentials in hippocampal CA3 neurons of SER. A higher dose of vigabatrin (10 mM) sometimes inhibited the first spike. However, vigabatrin at doses up to 10 mM did not significantly affect the single action potential elicited by stimulation of the mossy fibers in the hippocampal CA3 neurons of age-matched Wistar rats. In addition, application of vigabatrin (10 mM) did not significantly affect the firing induced by depolarizing pulse applied in the CA3 neurons of the SER, nor the miniature excitatory postsynaptic potential (mEPSP) recorded in the CA3 neurons of SER. The inhibitory effect of vigabatrin (1 mM) on the mossy fiber stimulation-induced depolarization shift with repetitive firing was blocked by concomitant application of bicuculline (10 microM), a GABA(A) receptor antagonist. These findings strongly suggested that GABA increased by inhibition of GABA transaminase with vigabatrin inhibits abnormal excitation of hippocampal CA3 neurons of SER via GABA(A) receptors, although the possibility that the drug acted directly on the GABA(A) receptors of CA3 neurons could not be completely excluded.

Action Potentials↗
PubMed1990

The slow inhibitory postsynaptic potential in rat hippocampal CA1 neurones is blocked by intracellular injection of QX-314.

Intracellular recordings were made from CA1 pyramidal neurones in the rat hippocampus slice preparation. The recording electrodes contained potassium acetate (4 M) with or without the quaternary lidocaine derivative, QX-314 (50 mM). Both fast (f) and slow (s) inhibitory postsynaptic potentials (IPSP) were evoked by low-frequency orthodromic stimulation. The s-IPSP was rapidly reduced by QX-314 injection. It decreased along a similar time course to the dV/dt of the action potential (AP). The f-IPSP and excitatory postsynaptic potential were not significantly reduced in size at a time when the s-IPSP was virtually abolished by QX-314. It is concluded that conductance through the K+ channels which are coupled to GABAB receptors is readily blocked by QX-314, while the Cl- channels which are coupled to GABAA receptors and the cation channels coupled to the glutamate receptors are relatively resistant to the local anaesthetic.

Action Potentials↗
PubMed2005

Acquisition of ischemic tolerance by repetitive transcranial magnetic stimulation in the rat hippocampus.

We investigated the acquisition of ischemic tolerance in the rat hippocampus using repetitive transcranial magnetic stimulation (rTMS). Rats received 1000 pulses/day for 7 days, and the field excitatory postsynaptic potentials were measured in the hippocampal CA1. After slices were exposed to ischemic conditions, long-term potentiation (LTP) was induced. The LTP of the stimulated group was enhanced compared with the LTP of the sham control group in each ischemic condition, suggesting that rTMS has the potential to protect hippocampal function from ischemia.

Animals↗
PubMed2006

Cellular mechanisms underlying antiepileptic effects of low- and high-frequency electrical stimulation in acute epilepsy in neocortical brain slices in vitro.

Approximately 30% of epilepsy patients suffer from drug-resistant epilepsy. Direct electrical stimulation of the epileptogenic zone is a potential new treatment modality for this devastating disease. In this study, we investigated the effect of two electrical stimulation paradigms, sustained low-frequency stimulation and short trains of high-frequency stimulation, on epileptiform discharges in neocortical brain slices treated with either bicuculline or magnesium-free extracellular solution. Sustained low-frequency stimulation (5-30 min of 0.1- to 5-Hz stimulation) prevented both interictal-like discharges and seizure-like events in an intensity-, frequency-, and distance-dependent manner. Short trains of high-frequency stimulation (1-5 s of 25- to 200-Hz stimulation) prematurely terminated seizure-like events in a frequency-, intensity-, and duration-dependent manner. Roughly one half the seizures terminated within the 100-Hz stimulation train (P < 0.01 compared with control), whereas the remaining seizures were significantly shortened by 53 +/- 21% (P < 0.01). Regarding the cellular mechanisms underlying the antiepileptic effects of electrical stimulation, both low- and high-frequency stimulation markedly depressed excitatory postsynaptic potentials (EPSPs). The EPSP amplitude decreased by 75 +/- 3% after 10-min, 1-Hz stimulation and by 86 +/- 6% after 1-s, 100-Hz stimulation. Moreover, partial pharmacological blockade of ionotropic glutamate receptors was sufficient to suppress epileptiform discharges and enhance the antiepileptic effects of stimulation. In conclusion, this study showed that both low- and high-frequency electrical stimulation possessed antiepileptic effects in the neocortex in vitro, established the parameters determining the antiepileptic efficacy of both stimulation paradigms, and suggested that the antiepileptic effects of stimulation were mediated mostly by short-term synaptic depression of excitatory neurotransmission.

2-Amino-5-phosphonovalerate↗
PubMed2006

Effects of melatonin on synaptic transmission and long-term potentiation in two areas of mouse hippocampus.

We have examined the effects of melatonin on synaptic transmission and long-term potentiation (LTP) in the Schaffer Collateral-CA1 and the mossy fiber-CA3 pathways in mouse hippocampus brain slices. Melatonin (0.1-1 mM) application had different actions on both the field excitatory postsynaptic potentials (fEPSPS) and LTP in the CA1 as compared to the CA3. In CA1, 0.1 mM melatonin blocked LTP, while 1 mM melatonin also depressed the fEPSP. In CA3, neither 0.1 nor 1 mM melatonin altered the fEPSP, whereas both concentrations only slightly reduced LTP. These results demonstrate that melatonin significantly alters synaptic transmission and LTP in the CA1 but has only modest actions in CA3.

Animals↗
PubMed2003

Altered synaptic and electrical properties of lumbar motoneurons in the neurological glial mutant taiep rat.

Maturation and differentiation of electrical properties of neurons and synaptic transmission are modulated by neuronal interaction. In vitro experiments have shown that these processes also seem to be regulated by signals from non-neuronal elements such as glial cells. It is not known, however, whether glial alterations in intact neural networks may also affect the maturation of electrical properties and synaptic transmission during development. We used the taiep rat, a neurological mutant with a progressive demyelination and astrogliosis, as an experimental model to study the postnatal development of motoneurons in an altered glial environment. Using the patch-clamp technique, we made intracellular recording from motoneurons of Rexed's lamina IX in spinal cord slices of neonatal rats (postnatal day P4-P10). The electrical properties of normal motoneurons changed significantly with age, showing decreasing input resistance (R(in)) and increasing membrane capacity (C(m)). The rheobase increased with age, accompanied by an increase of the amplitude and a decrease of the duration of action potentials (APs). In contrast, mutant neurons showed no age-dependent changes of R(in), C(m), or AP characteristics. After blocking inhibitory transmission, intralaminar bipolar stimulation elicited, in both control and taiep motoneurons, fast glutamatergic excitatory postsynaptic potentials (EPSPs). Two types of taiep motoneurons were identified according to the temporal patterns of synaptic responses; (1). taiep(SYN) neurons, which showed no significant differences to control motoneurons, and (2). taiep(ASYN) neurons, in which the initial EPSP was followed by a variable number of delayed, asynchronous EPSP responses (for up to 300 ms). All these electrophysiological findings suggest that the mutation in taiep rats interfered with the development of the electrical properties of neurons and with the maturation of synaptic transmission, probably due to alterations in the neuron-glia interactions.

Action Potentials↗
PubMed1999

N-ethylmaleimide selectively blocks presynaptic GABA-B autoreceptor but not heteroreceptor-mediated inhibition in adult rat striatal slices.

Intracellular recording techniques were used in slices of adult rat striatum to compare the sensitivity of presynaptic gamma-aminobutyric acid type B (GABA-B) autoreceptor and heteroreceptor-mediated inhibition to the sulfhydryl alkylating agent, N-ethylmaleimide (NEM). NEM (100 microM) alone had no significant effect on resting potential or input resistance and did not consistently effect stimulus-evoked responses. Treatment of slices with NEM for up to 1 h, either in the presence or the absence of the GABA-B receptor-specific agonist, baclofen (BAC; 100 microM), completely blocked the BAC-induced depression of inhibitory, but not excitatory, postsynaptic potentials. This differential sensitivity to NEM alkylation suggests that in the adult rat striatum, the presynaptic GABA-B autoreceptors and heteroreceptors may exhibit distinct receptor-effector coupling mechanisms.

Animals↗
PubMed2001

Synaptically activated calcium responses in dendrites of hippocampal oriens-alveus interneurons.

Activation of metabotropic glutamate receptors (mGluRs) by agonists increases intracellular calcium levels ([Ca(2+)](i)) in interneurons of stratum oriens/alveus (OA) of the hippocampus. We examined the mechanisms that contribute to dendritic Ca(2+) increases in these interneurons during agonist activation of mGluRs and during synaptically evoked burst discharges, using simultaneous whole cell recordings and confocal Ca(2+) imaging in rat hippocampal slices. First, we found that the group I/II mGluR agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD; 100 microM) increased dendritic [Ca(2+)](i) and depolarized OA interneurons. Dendritic Ca(2+) responses were correlated with membrane depolarizations, but Ca(2+) responses induced by ACPD were larger in amplitude than those elicited by equivalent somatic depolarization. Next, we used linescans to measure changes in dendritic [Ca(2+)](i) during synaptically evoked burst discharges and somatically elicited repetitive firing in disinhibited slices. Dendritic Ca(2+) signals and electrophysiological responses were stable over repeated trials. Peak Ca(2+) responses were linearly related to number and frequency of action potentials in burst discharges for both synaptic and somatic stimulation, but the slope of the relationship was steeper for responses evoked somatically. Synaptically evoked [Ca(2+)](i) rises and excitatory postsynaptic potentials were abolished by antagonists of ionotropic glutamate receptors. The group I/II mGluR antagonist S-alpha-methyl-4-carboxyphenylglycine (500 microM) produced a significant partial reduction of synaptically evoked dendritic Ca(2+) responses. The mGluR antagonist did not affect synaptically evoked burst discharges and did not reduce either Ca(2+) responses or burst discharges evoked somatically. Therefore ionotropic glutamate receptors appear necessary for synaptically evoked dendritic Ca(2+) responses, and group I/II mGluRs may contribute partially to these responses. Dendritic [Ca(2+)](i) rises mediated by both ionotropic and metabotropic glutamate receptors may be important for synaptic plasticity and the selective vulnerability to excitotoxicity of OA interneurons.

Animals↗
PubMed2003

Synaptic plasticity preserved with arachidonic acid diet in aged rats.

We examined whether synaptic plasticity was preserved in aged rats administered an arachidonic acid (AA) containing diet. Young male Fischer-344 rats (2 mo of age), and two groups of aged rats of the same strain (2 y of age) who consumed either a control diet or an AA ethyl ester-containing diet for at least 3 mo were used. In the Morris water maze task, aged rats on the AA diet had tendency to show better performance than aged rats on the control diet. Long-term potentiation induced by tetanic stimulation was recorded from a 300 microm thick hippocampal slice with a 36 multi-electrode-array positioned at the dendrites of CA1 pyramidal neurons. The degree of potentiation after 1 h in aged rats on the AA diet was comparable as that of young controls. Phospholipid analysis revealed that AA and docosahexaenoic acid were the major fatty acids in the hippocampus in aged rats. There was a correlation between the behavioral measure and the changes in excitatory postsynaptic potential slope and between the physiologic measure and the total amount of AA in hippocampus.

Aging↗